tbuckley/cabot-search huggingface dataset:
Complete Femoral Osteonecrosis in the Setting of Myelodysplastic Syndrome
Authors: Isaac Kargar Samani, Yassin Akachar, Bruno Krug
Journal: Clinical Nuclear Medicine (2023)

Abstract A 76-year-old man was diagnosed with a hematological neoplasm combining myelodysplastic and myeloproliferative characteristics back in July 2021. Five months after the diagnosis, his condition got more severe when the blasts rose up to 14%, so he was started on hypomethylating agent–based therapy. A few weeks later, the patient was hospitalized after developing fever and a pain in the right thigh. To exclude any source of occult infection, an 18 F-FDG PET/CT was performed. FDG PET/CT showed a complete lack of metabolism in the right femur. An MRI and a biopsy confirmed the suspected diagnosis of osteonecrosis.
Unilateral tests of lower-limb function as prognostic indicators of future knee-related outcomes following anterior cruciate ligament injury: a systematic review and meta-analysis of 13 150 adolescents and adults
Authors: Thomas J West, Andrea M Bruder, Kay M Crossley, Adam G Culvenor
Journal: British Journal of Sports Medicine (2023)

Objective To investigate the prognostic capacity of individual hop tests, hop test batteries and other unilateral functional performance tests following anterior cruciate ligament (ACL) injury. Design Systematic review with meta-analysis. Data sources Six databases searched up to June 2021. Eligibility criteria Studies reporting associations between unilateral lower-limb function (eg, hop tests) following ACL injury and future (≥3 months) knee-related outcomes. Results Of 42 included studies (13 150 participants), all assessed the single-forward hop test and 32 assessed a repeated-forward hop test (crossover hop, triple hop, 6m-timed hop), mostly within a year after ACL injury/reconstruction. Results of meta-analyses indicated that higher single-forward and repeated-forward hop limb symmetry were associated with higher odds of return-to-sport 1–3 years post-ACL reconstruction (OR 2.15; 95% CI 1.30 to 3.54; OR 2.11; 95% CI 1.23 to 3.60, respectively). Higher single-forward and repeated-forward hop limb symmetry was associated with better self-reported symptoms and function 1–37 years after ACL injury (OR 2.51; 95% CI 1.62 to 3.88; OR 4.28; 95% CI 1.65 to 11.08, respectively). Higher limb symmetry on a repeated-forward hop does not appear to be associated with higher odds of successful rehabilitation without ACL reconstruction (OR 1.51; 95% CI 0.94 to 2.44). Achieving ≥90% limb symmetry on the single-forward hop was associated with reduced odds of knee osteoarthritis 5–37 years after ACL injury (OR 0.46; 95% CI 0.23 to 0.94). Conclusion Very low certainty evidence suggests single-forward and repeated-forward hop tests are prognostic indicators for important knee-related outcomes in individuals after ACL injury and may help stratify individuals at risk of poor outcomes to target rehabilitation interventions. PROSPERO registration number CRD42018092197.
Pharmacological Inhibition of the NLRP3 Inflammasome: Structure, Molecular Activation, and Inhibitor-NLRP3 Interaction
Authors: Qiang Ma
Journal: Pharmacological Reviews (2023)

The nucleotide-binding, oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multi-protein complex that combines sensing, regulation, and effector functions to regulate inflammation in health and disease. NLRP3 is activated by a diverse range of inflammation-instigating signals known as pathogen associated molecular patterns and danger associated molecular patterns. Upon activation, NLRP3 oligomerizes and recruits partner proteins to form a supramolecular platform to process the maturation and release of interleukin (IL)-1β, IL-18, and gasdermin D, major mediators of inflammation and inflammatory cell death termed pyroptosis. The NLRP3 inflammasome has been implicated in the pathogenesis of a wide range of disease conditions, including chronic inflammatory disease that are associated with lifestyle and dietary changes, aging, and environmental exposures and have become the leading cause of death worldwide. Pharmacological targeting of NLRP3 and signaling demonstrated promising efficacy in ameliorating a list of disease conditions in animal models. These findings underscore the potential and importance of NLRP3 as a druggable target for treating a range of diseases. In this review, recent progress in understanding the structure and mechanism of action of the NLRP3 inflammasome is discussed with focus on pharmacological inhibition of NLRP3 by small molecule inhibitors. New structural and mechanistic insights into NLRP3 activation and inhibitor-NLRP3 interactions would aid in the rational design and pharmacological evaluation of NLRP3 inhibitors for treatment of human disease. <b>Significance Statement</b> The NLRP3 inflammasome plays central role in innate immune sensing and control of inflammation. Pharmacological inhibition of NLRP3 demonstrated promising efficacy in a range of diseases in animal models. Recent elucidation of the structure and inhibitor binding of NLRP3 generated new insights into its mode of action and inhibitor-NLRP3 interaction at molecular levels, providing new framework for developing small chemical inhibitors of NLRP3 with improved efficacy and specificity against chronic disease that has become major health concerns worldwide.
Tubular Epithelial Cell HMGB1 Promotes AKI-CKD Transition by Sensitizing Cycling Tubular Cells to Oxidative Stress: A Rationale for Targeting HMGB1 during AKI Recovery
Authors: Zhi Bo Zhao, Julian A. Marschner, Takamasa Iwakura, Chenyu Li, Manga Motrapu, Meisi Kuang, Bastian Popper, Andreas Linkermann, Jan Klocke, Philipp Enghard, Yoshiharu Muto, Benjamin D. Humphreys, Helena Erlandsson Harris, Paola Romagnani, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Cells undergoing necrosis release extracellular high mobility group box (HMGB)-1, which triggers sterile inflammation upon AKI in mice. Neither deletion of HMGB1 from tubular epithelial cells, nor HMGB1 antagonism with small molecules, affects initial ischemic tubular necrosis and immediate GFR loss upon unilateral ischemia/reperfusion injury (IRI). On the contrary, tubular cell-specific HMGB1 deficiency, and even late-onset pharmacological HMGB1 inhibition, increased functional and structural recovery from AKI, indicating that intracellular HMGB1 partially counters the effects of extracellular HMGB1. In vitro studies indicate that intracellular HMGB1 decreases resilience of tubular cells from prolonged ischemic stress, as in unilateral IRI. Intracellular HMGB1 is a potential target to enhance kidney regeneration and to improve long-term prognosis in AKI. Background Late diagnosis is a hurdle for treatment of AKI, but targeting AKI-CKD transition may improve outcomes. High mobility group box-1 (HMGB1) is a nuclear regulator of transcription and a driver of necroinflammation in AKI. We hypothesized that HMGB1 would also modulate AKI-CKD transition in other ways. Methods We conducted single-cell transcriptome analysis of human and mouse AKI and mouse in vivo and in vitro studies with tubular cell-specific depletion of Hmgb1 and HMGB1 antagonists. Results HMGB1 was ubiquitously expressed in kidney cells. Preemptive HMGB1 antagonism with glycyrrhizic acid (Gly) and ethyl pyruvate (EP) did not affect postischemic AKI but attenuated AKI-CKD transition in a model of persistent kidney hypoxia. Consistently, tubular Hmgb1 depletion in Pax8 rtTA, TetO Cre, Hmgb1 fl/fl mice did not protect from AKI, but from AKI-CKD transition. In vitro studies confirmed that absence of HMGB1 or HMGB1 inhibition with Gly and EP does not affect ischemic necrosis of growth-arrested differentiated tubular cells but increased the resilience of cycling tubular cells that survived the acute injury to oxidative stress. This effect persisted when neutralizing extracellular HMGB1 with 2G7. Consistently, late-onset HMGB1 blockade with EP started after the peak of ischemic AKI in mice prevented AKI-CKD transition, even when 2G7 blocked extracellular HMGB1. Conclusion Treatment of AKI could become feasible when ( 1 ) focusing on long-term outcomes of AKI; ( 2 ) targeting AKI-CKD transition with drugs initiated after the AKI peak; and ( 3 ) targeting with drugs that block HMGB1 in intracellular and extracellular compartments.
Lineage Tracing and Single-Nucleus Multiomics Reveal Novel Features of Adaptive and Maladaptive Repair after Acute Kidney Injury
Authors: Louisa M.S. Gerhardt, Kari Koppitch, Jordi van Gestel, Jinjin Guo, Sam Cho, Haojia Wu, Yuhei Kirita, Benjamin D. Humphreys, Andrew P. McMahon
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Understanding the mechanisms underlying adaptive and maladaptive renal repair after AKI and their long-term consequences is critical to kidney health. The authors used lineage tracing of cycling cells and single-nucleus multiomics (profiling transcriptome and chromatin accessibility) after AKI. They demonstrated that AKI triggers a cell-cycle response in most epithelial and nonepithelial kidney cell types. They also showed that maladaptive proinflammatory proximal tubule cells (PTCs) persist until 6 months post-AKI, although they decreased in abundance over time, in part, through cell death. Single-nucleus multiomics of lineage-traced cells revealed regulatory features of adaptive and maladaptive repair. These included activation of cell state–specific transcription factors and cis-regulatory elements, and effects in PTCs even after adaptive repair, weeks after the injury event. Background AKI triggers a proliferative response as part of an intrinsic cellular repair program, which can lead to adaptive renal repair, restoring kidney structure and function, or maladaptive repair with the persistence of injured proximal tubule cells (PTCs) and an altered kidney structure. However, the cellular and molecular understanding of these repair programs is limited. Methods To examine chromatin and transcriptional responses in the same cell upon ischemia-reperfusion injury (IRI), we combined genetic fate mapping of cycling ( Ki67 + ) cells labeled early after IRI with single-nucleus multiomics—profiling transcriptome and chromatin accessibility in the same nucleus—and generated a dataset of 83,315 nuclei. Results AKI triggered a broad cell cycle response preceded by cell type–specific and global transcriptional changes in the nephron, the collecting and vascular systems, and stromal and immune cell types. We observed a heterogeneous population of maladaptive PTCs throughout proximal tubule segments 6 months post-AKI, with a marked loss of maladaptive cells from 4 weeks to 6 months. Gene expression and chromatin accessibility profiling in the same nuclei highlighted differences between adaptive and maladaptive PTCs in the activity of cis-regulatory elements and transcription factors, accompanied by corresponding changes in target gene expression. Adaptive repair was associated with reduced expression of genes encoding transmembrane transport proteins essential to kidney function. Conclusions Analysis of genome organization and gene activity with single-cell resolution using lineage tracing and single-nucleus multiomics offers new insight into the regulation of renal injury repair. Weeks to months after mild-to-moderate IRI, maladaptive PTCs persist with an aberrant epigenetic landscape, and PTCs exhibit an altered transcriptional profile even following adaptive repair.
Intensive BP Control in Patients with CKD and Risk for Adverse Outcomes
Authors: Elaine Ku, Charles E. McCulloch, Lesley A. Inker, Hocine Tighiouart, Franz Schaefer, Elke Wühl, Piero Ruggenenti, Giuseppe Remuzzi, Barbara A. Grimes, Mark J. Sarnak
Journal: Journal of the American Society of Nephrology (2023)

Background The effect of intensive BP lowering (to systolic BP of &lt;120 mm Hg) on the risk of kidney failure requiring KRT remains unclear in patients with advanced CKD. Such patients were not well-represented in trials evaluating intensive BP control. Methods To examine the effect of intensive BP lowering on KRT risk—or when not possible, trial-defined kidney outcomes—we pooled individual-level data from seven trials that included patients with eGFR&lt;60 ml/min per 1.73 m 2 . We performed prespecified subgroup analyses to evaluate the effect of intensive BP control by baseline albuminuria and eGFR (CKD stages 4–5 versus stage 3). Results Of 5823 trial participants, 526 developed the kidney outcome and 382 died. Overall, intensive (versus usual) BP control was associated with a lower risk of kidney outcome and death in unadjusted analyses but these findings did not achieve statistical significance. However, the intervention's effect on the kidney outcome differed depending on baseline eGFR ( P interaction=0.05). By intention-to-treat analysis, intensive (versus usual) BP control was associated with a 20% lower risk of the primary kidney outcome in those with CKD GFR stages 4–5, but not in CKD GFR stage 3. There was no interaction between intensive BP control and the severity of albuminuria for kidney outcomes. Conclusions Data from this pooled analysis of seven trials suggest a benefit of intensive BP control in delaying KRT onset in patients with stages 4–5 CKD but not necessarily with stage 3 CKD. These findings suggest no evidence of harm from intensive BP control, but also point to the need for future trials of BP targets focused on populations with advanced kidney disease.
Prenatal antibiotic use and subsequent risk of atopic eczema
Authors: Terrence M Vance, Tricia Li, Eunyoung Cho, Aaron M Drucker, Carlos A Camargo, Abrar A Qureshi
Journal: British Journal of Dermatology (2022)

Journal Article Prenatal antibiotic use and subsequent risk of atopic eczema Get access Terrence M Vance, Terrence M Vance Department of Dermatology, Warren Alpert Medical School of Brown UniversityDepartment of Epidemiology, School of Public Health, Brown University, Providence, RI, USA Correspondence: Terrence M. Vance. Email: terrence_vance@brown.edu Search for other works by this author on: Oxford Academic Google Scholar Tricia Li, Tricia Li Department of Dermatology, Warren Alpert Medical School of Brown University Search for other works by this author on: Oxford Academic Google Scholar Eunyoung Cho, Eunyoung Cho Department of Dermatology, Warren Alpert Medical School of Brown UniversityDepartment of Epidemiology, School of Public Health, Brown University, Providence, RI, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School Search for other works by this author on: Oxford Academic Google Scholar Aaron M Drucker, Aaron M Drucker Department of Dermatology, Warren Alpert Medical School of Brown UniversityDivision of Dermatology, Department of Medicine, University of Toronto, Toronto, CanadaWomen's College Research Institute and Department of Medicine, Women's College Hospital, Toronto, Canada Search for other works by this author on: Oxford Academic Google Scholar Carlos A Camargo, Jr, Carlos A Camargo, Jr Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical SchoolDepartment of Emergency Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USADepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA Search for other works by this author on: Oxford Academic Google Scholar Abrar A Qureshi Abrar A Qureshi Department of Dermatology, Warren Alpert Medical School of Brown UniversityDepartment of Epidemiology, School of Public Health, Brown University, Providence, RI, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 188, Issue 4, April 2023, Pages 561–563, https://doi.org/10.1093/bjd/ljac108 Published: 27 December 2022 Article history Received: 29 September 2022 Revision received: 17 October 2022 Published: 27 December 2022 Corrected and typeset: 23 January 2023
Corrigendum to: International consensus definition of disease flare in hidradenitis suppurativa
Journal: British Journal of Dermatology (2023)

Using gene expression and proteomic studies, Toll-like receptor 2 has been found to play a role in epidermal hyperkeratosis and the development of congenital ichthyosis. Downstream signalling involving GATA-3 reveals potential novel drug targets for congenital ichthyosis. Further studies of ichthyosis subtypes will provide more precise strategies for targeted therapies.
The association between pilonidal sinus disease and hidradenitis suppurativa: a systematic review and meta-analysis
Authors: Kirsty J L Wark, Samuel A Der Sarkissian, Artiene Tatian, Jane Woods, Geoffrey D Cains
Journal: British Journal of Dermatology (2022)

We performed a systematic review and meta-analysis examining the association between hidradenitis suppurativa (HS) and pilonidal sinus disease (PSD). We found a strong association between HS and PSD, with an increased occurrence of PSD in individuals with HS compared with unaffected controls. Given this strong association, patients with HS should be assessed for PSD.
Online behavioural interventions for children and young people with atopic eczema: refining the way forward
Authors: Parker Magin, Katie Fisher
Journal: British Journal of Dermatology (2022)

The online behavioural interventions for children and young people with atopic eczema evaluated in the article reviewed in this commentary have previously been found to be efficacious. A process evaluation, reported in the article, explored how and why the interventions have worked.
Association between age at symptom onset and disease severity in older patients with hidradenitis suppurativa
Authors: Simon W Jiang, Amy J Petty, Jennifer L Jacobs, Camille Robinson, Sravya M Bhatia, Jeffery T Kwock, Beiyu Liu, Cynthia L Green, Russell P Hall, Adela R Cardones, Tarannum Jaleel
Journal: British Journal of Dermatology (2023)

Journal Article Association between age at symptom onset and disease severity in older patients with hidradenitis suppurativa Get access Simon W Jiang, Simon W Jiang Department of Dermatology and https://orcid.org/0000-0002-9509-9001 Search for other works by this author on: Oxford Academic Google Scholar Amy J Petty, Amy J Petty Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar Jennifer L Jacobs, Jennifer L Jacobs Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar Camille Robinson, Camille Robinson Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar Sravya M Bhatia, Sravya M Bhatia Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar Jeffery T Kwock, Jeffery T Kwock Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar Beiyu Liu, Beiyu Liu Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27701, USA Search for other works by this author on: Oxford Academic Google Scholar Cynthia L Green, Cynthia L Green Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27701, USA Search for other works by this author on: Oxford Academic Google Scholar Russell P Hall, Russell P Hall Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar Adela R Cardones, Adela R Cardones Kansas University Medical Center, Kansas City, KS 66160, USA Search for other works by this author on: Oxford Academic Google Scholar ... Show more Tarannum Jaleel Tarannum Jaleel Department of Dermatology and Correspondence: Tarannum Jaleel. Email: tarannum.jaleel@duke.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 188, Issue 4, April 2023, Pages 555–576, https://doi.org/10.1093/bjd/ljac121 Published: 03 January 2023 Article history Accepted: 17 December 2022 Published: 03 January 2023 Corrected and typeset: 30 January 2023
Dermatology Quality of Life Index scores in Bangladeshi patients with atopic eczema and their families in East London
Authors: Soha S Tawfik, Bjorn R Thomas, David P Kelsell, Jonathan Grigg, Edel A O’Toole
Journal: British Journal of Dermatology (2022)

Atopic eczema (AE) is a chronic relapsing, pruritic disease that greatly affects the child and family's quality of life (QoL). It is usually common and severe among children of Bangladeshi ethnicity.This is a cross-sectional quantitative study in patients with AE of Bangladeshi origin, which aims to analyse different components of the family, children and adult quality-of-life indices and their relationship to patient age, sex, eczema severity and distribution, other allergic associations, parental education and socioeconomic level.Children and young adults of Bangladeshi origin aged 0-30 years, clinically diagnosed with AE were recruited as part of the Tower Hamlets Eczema Assessment project, a clinical phenotyping study of AE in the Bangladeshi population living in East London. Questionnaires completed by children/parents included the Family Dermatology Life Quality Index (FDLQI), Infant's Dermatology Quality of Life (IDQOL) and the Children's Dermatology Life Quality Index (CDLQI). Young adults completed the Dermatology Life Quality Index (DLQI). The disease severity was assessed objectively using the Eczema Area Severity Index (EASI). Patients and parents who did not read or speak English were aided by Bengali/Sylheti-speaking research assistants.Overall, 460 Bangladeshi children and 98 adults with AE were recruited. Burden of care, extra housework and emotional distress were the highest affected domains in parental QoL, while itching and sleep were the highest for children. Significant factors influencing FDLQI score were EASI [marginal effect (ME) 1.01, 95% confidence interval (CI) 1.00-1.03; P = 0.004], age (ME 0.98, 95% CI 0.97-0.99; P = 0.004), extensor eczema distribution (ME 1.25, 95% CI 1.03-1.52; P = 0.023), parental English fluency (ME 1.29, 95% CI 1.10-1.52; P = 0.002) and atopic comorbidities (ME 1.10, 95% CI 1.04-1.17; P = 0.001). Parental socioeconomic class was a nonsignificant factor. IDQOL/CDLQI was influenced significantly by the child's age (ME 0.99, 95% CI 0.97-1.00, P = 0.023), 'nonclear' eczema distribution clusters especially the 'severe extensive' cluster (ME 1.46, 95% CI 1.15-1.84; P = 0.002) and nonsignificantly by EASI and parental English literacy and socioeconomic levels. DLQI was affected significantly by nonclear eczema distribution groups especially 'severe extensive' (ME 2.49, 95% 1.76-3.53; P < 0.001) and nonsignificantly by patient age, and female sex.AE is a chronic disease where many external factors other than disease severity affect QoL of patients and their families, -especially in under-represented minority groups who face different linguistic and cultural barriers.